Review Finds Mediterranean Diet Benefits May Come from How Foods Work Together

The Mediterranean Diet’s health benefits, documented by decades of research, may owe more to the interaction among its foods than to any single ingredient.

A major review published in the British Journal of Pharmacology suggests that olive oil, vegetables, legumes, fruits, nuts and fish interact across multiple biological pathways linked to inflammation, metabolism, vascular function and aging.

We have reached a point where we are discussing increasingly small biological details, but we already know what the overall effect is.– Vincenza Gianfredi, professor at the University of Padua, Italy

The review, authored by a team of European scientists, examines how the components of the Med Diet work together to produce its well-documented benefits.

“The biological mechanisms are multiple,” Vincenza Gianfredi, a public health professor at the University of Padua who was not involved in the study, told Olive Oil Times after reviewing the findings.

“The micronutrient that determines an effect is influenced by a large number of other factors, including genetics, environmental exposures and lifestyle,” she added. “The Mediterranean diet is not only what I put on my plate. It is also how I live, how I interact with others and even factors such as stress.”

While the review reinforces evidence linking the Mediterranean Diet to lower risks of several diseases, including cardiovascular conditions, cancer and dementia, Gianfredi said the most interesting aspect is not the expanding list of associated benefits.

Instead, she said, the review shows how researchers are gaining a more detailed understanding of the biological systems involved.

“Even though I often hear people say that when we talk about the Mediterranean diet everything is already established, I don’t completely agree,” she said. “We have reached a point where we are discussing increasingly small biological details, but we already know what the overall effect is.”

One of the review’s central arguments is that the Mediterranean Diet functions less as a collection of healthy foods than as a coordinated biological system in which different foods influence many of the same pathways.

Polyphenols from extra virgin olive oil, omega-3 fatty acids from fish, dietary fiber from legumes and whole grains, and bioactive compounds from fruits and vegetables all appear to converge on mechanisms associated with chronic inflammation, oxidative stress, insulin sensitivity and endothelial function.

In other words, the same biological processes may be influenced simultaneously by multiple components of the dietary pattern.

“Oxidative stress and chronic low-grade inflammation are linked, just as nitric oxide and endothelial function are linked,” Gianfredi said.

Nitric oxide is a signaling molecule that helps blood vessels dilate and maintain healthy vascular function. “Very often they activate the same molecules and biological pathways,” she added. “Even the same molecule can be involved in multiple mechanisms of action.”

The review shows how olive oil polyphenols, omega-3 fatty acids and dietary fiber appear to influence overlapping pathways related to inflammation, oxidative stress, metabolism and vascular health.

This shared effect appears to focus on specific molecular targets. The review highlights how olive oil polyphenols, omega-3s and plant compounds target the same cellular “switches,” including the NF-κB pathway and the NLRP3 inflammasome, two well-known molecular drivers of chronic inflammation.

By acting on these systems from different angles, the foods may work in tandem to help regulate the body’s inflammatory responses.

As a result, the review suggests that Mediterranean Diet foods may act less as isolated ingredients than as parts of a coordinated biological network.

Unlike many other Mediterranean foods, extra virgin olive oil emerges as a recurring protagonist throughout the review.

The authors describe EVOO as a cornerstone of the Mediterranean Diet because its monounsaturated fats and rich mix of polyphenols appear to influence multiple pathways simultaneously, from inflammation and oxidative stress to vascular function, metabolic health and cellular aging.

They also point to oleic acid, the primary fat in EVOO, as a direct activator of Sirtuin 1, a protein involved in cellular stress responses, mitochondrial metabolism and aging.

The review links higher olive oil consumption to lower risks of cardiovascular disease and type 2 diabetes, along with improvements in glycemic control, blood pressure and inflammatory markers.

“Olive oil is absolutely one of the fundamental foods of the Mediterranean diet, both because it is the principal source of fats and because it is rich in many of the micronutrients whose biological mechanisms are discussed throughout the paper,” Gianfredi said.

At the same time, she warned against viewing olive oil in isolation.

“We should not confuse extra virgin olive oil with a miraculous food,” Gianfredi said. “It still belongs to the fat group. It should be consumed in the recommended quantities. It is not that because it is beneficial we can consume unlimited amounts of it.”

Researchers describe how olive oil polyphenols, omega-3 fatty acids and numerous plant compounds appear to influence inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha and C-reactive protein.

Many of these compounds also affect oxidative stress pathways, further reinforcing the interaction between the two systems.

“We can be very confident in saying that one of the principal ways through which the Mediterranean diet exerts its beneficial effects is its anti-inflammatory action,” Gianfredi said.

“It acts against what we call chronic low-grade inflammation, which is involved in the development of most chronic degenerative diseases that are now extremely common in the population.”

The review goes further, exploring less-established but increasingly studied pathways involving the gut microbiota, telomere stability, epigenetic regulation and cellular aging.

Telomeres are protective caps at the ends of chromosomes and are often considered a marker of biological aging. The review discusses emerging evidence that components of the Mediterranean Diet may help protect them by limiting oxidative damage and chronic inflammation.

However, the authors caution that much of the evidence on telomeres, DNA protection and epigenetic changes still comes from laboratory and animal studies.

They also note that differences in gut microbiota may influence how effectively individuals absorb and metabolize olive oil polyphenols and other bioactive compounds.

Although much of this evidence remains preliminary, the authors suggest these mechanisms may help explain why adherence to the Mediterranean Diet has repeatedly been associated not only with lower disease risk but also with healthier aging.

“We see eighty-year-olds who are in excellent health and eighty-year-olds who are bedridden,” Gianfredi said. “That means something is influencing the trajectory of aging.”

“Following a Mediterranean dietary pattern not only helps prevent disease, but even when a disease is present it can slow its progression,” she added. “It is not a drug, but it contributes to maintaining a good state of health.”

“An individual may maintain cognitive autonomy for longer,” Gianfredi continued. “And thanks to the reduction in other health conditions, they may also maintain physical autonomy for longer.”

Yet while scientific understanding of the Mediterranean Diet continues to deepen, Gianfredi believes the biggest challenge facing researchers may no longer be biological.

“The question today is no longer why the Mediterranean diet works,” she said. “The question is how we can communicate this information and, above all, make sure people actually follow it.”

A global analysis of dietary patterns between 1960 and 2011 found that adherence to the Mediterranean Diet declined sharply across much of the Mediterranean basin during the second half of the twentieth century.

While the decline later stabilized and some non-Mediterranean countries showed signs of improvement, the authors concluded that many Mediterranean nations had moved substantially away from their traditional dietary pattern.

A separate study conducted in Southern Italy found a significant decline in adherence to the Mediterranean Diet between the mid-1980s and mid-2000s, with the steepest reductions occurring among younger adults.

Perhaps most strikingly, researchers reported that the most dramatic dietary change involved olive oil consumption itself.

“For a thesis project, we analyzed food advertising in Italy and found that advertisements promoting healthy foods were practically nonexistent,” Gianfredi said.

“Today we live in a productivity-driven society where every minute of our time is expected to produce something,” she added. “We have lost the value of dedicating time to food.”

As evidence linking the Mediterranean Diet to better health outcomes continues to accumulate, the challenge may no longer be proving its benefits. It may be preserving the dietary pattern itself.

“There are countries outside the Mediterranean region that are increasing their adherence to the Mediterranean diet,” Gianfredi said. “Some Northern European countries are making significant progress while Italy is moving in the opposite direction.”

“That is why the central question today is no longer whether the Mediterranean diet works,” she concluded. “We need to ask which public health policies and strategies are necessary to preserve and promote it.”